Study On The Protection Effect Of Supramolecular Gel On The Photostability Of Drugs

Many drugs are unstable under illumination leading to the photochemical reactions. These reactions can cause the drugs less effective and generate some toxic end/intermediate products. Therefore the applications of these light sensitive drugs are limited. In present work we use the supramolecular organogels formed by the self-assembly of sorbitol-based gelators and the supramolecular hydrogels formed by the self-assembly of cystine derivative gelator as new durg carriers to protect photostability of some light sensitive drugs. Retinyl palmitate(RP)and hemin are employed as model drugs. The protection effect of supramolecular gel on the photostability of RP and hemin and the diffusion behavior of RP in supramolecular organogels have been studied. The mechanism of the protection effect has also been investigated. The results are as follows:1. Supramolecular organogels were prepared by the self-assembly of a series of sorbitol-based gelators (DBS, MDBS and DMDBS) in a solvent mixture of PEG400/ ethanol or 1,2-propylene glycol/ethanol as the drug carrier of RP. The relative activity of RP in supramolecular gel is about 60% higher than that in HEC( Hydroxyethyl cellulose) gel after 80 minutes of UV illumination. MDBS gels exhibited excellent protective effects on the photostability of RP. In both matrices of supramolecular gels, oligomer PEG400/ethanol shows a better protective effect than propylene glycol/ ethanol. It was found there is a matching concentration ratio between MDBS and RP in the supramolecular gels.2. The proposed mechanism of the protective effect of supramolucular gels was investigated by analysing the microstructure of the gels using SEM(Scanning electron microscope) and FOM(Fluorescence optical microscope). The data show that RP is located and isolated into the solvent chambers formed by the three- dimensional network structure. The isolation of RP in the chambers plays an important role to reduce the probability of collision of the photoactivated RP molecules. This may be the main reason for the protective effect of the supramolecular gels on the photostability of RP. The UV spectra of RP in the supramolecular gels and in the corresponding solutions indicated that the chemical structure and properties of RP have not been changed. 3. Supramolecular-micelle hydrogels were prepared by the self-assembly of N,N'- dibenzoyl-cystine (DBC) in micelle aqueous solution as the drug carrier of RP. Anionic surfactant SDBS and non-ionic surfactant Tween 80 are employed to enhance the solubility of RP in aqueous solution. Orthogonal experimental method L9(3~4)was used to optimize the components of supramolecular-micelle hydrogels for the best results. The relative activity of RP in SDBS and Tween 80 supramolecular-micelle hydrogel is about 80% and 60% higher than that in HEC gel after 6 minutes of UV illumination respectively.4. Supramolecular gels were prepared by the self-assembly of DBS, MDBS and DMDBS in a solvent mixture of 1,2-propylene glycol/water as the drug carrier of hemin. The photodegradation experiments of hemin were conducted under natrual light irradiation. The photostability of hemin protected by the supramolecular gels remained stable, while the photostability of hemin in aqueous solution decreased.5. Supramolecular gels were prepared by the self-assembly of DBS, MDBS and DMDBS in IPM as the drug carrier of RP. The diffusion behaviors of RP were affected by the structure and concentration of gelators, the concentration of RP and temperature significantly.